DETERMINATION AND METABOLISM OF DITHIOL CHELATING-AGENTS .15. THE MESO-2,3-DIMERCAPTOSUCCINIC ACID-CYSTEINE (1 2) MIXED DUSULFIDE, A MAJOR URINARY METABOLITE OF DMSA IN THE HUMAN, INCREASES THE URINARY-EXCRETION OF LEAD IN THE RAT/

Meso-2,3-dimercaptosuccinic acid (DMSA) in humans is an effective p.o. therapeutically useful chelating agent of Pb. In humans given DMSA p. o., the major urinary metabolite is DMSA-cysteine (1:2) mixed disulfid e. In order to determine its efficacy in mobilizing Pb and increasing urinary Pb excretion, the mixed disulfide was given to rats treated pr eviously with Pb acetate. The mixed disulfide was as effective as DMSA in increasing the urinary excretion of Pb and mobilizing Pb from the kidney. DMSA, however, appears to be superior for mobilizing Pb from t he liver and the brain. After the mixed disulfide was given s.c. to ra ts, DMSA was found in the blood and urine. Twenty-four hours after adm inistration, 0.7% of the administered mixed disulfide was found in the urine as DMSA, indicating the mixed disulfide can be reduced to DMSA. The mixed disulfide was also reduced in vitro to DMSA during incubati on with rat blood. Although in the rat the DMSA-cysteine (1:2) mixed d isulfide mobilized Pb from the kidney, increased the urinary excretion of Pb and was to some extent reduced to DMSA, its fate and pharmacolo gical properties in the human, where it is found after DMSA administra tion, are unknown.